Cyclopropyl cyclohexanes

ABSTRACT

CYCLOHEXANES AND CYCLOHEXANOLS HAVING A CYCLOPROPANE SUBSTITUENT ARE PREPARED FROM TERPENES AND DERIVATIVES THEREOF WHICH ARE USEFUL AS FRAGRANCES OR FLAVORS.

United States Patent O US. Cl. 260-631 R 3 Claims ABSTRACT OF THE DISCLOSURE Cyclohexanes and cyclohexanols having a cyclopropane substituent are prepared from terpenes and derivatives thereof which are useful as fragrances or flavors.

BACKGROUND OF THE DISCLOSURE Methanol and various derivatives thereof, including various terpene derivatives, are widely used as flavors and fragrances. Many of these are of natural origin but for commercial purposes the art has developed a number of synthetic products of related structure that either replace the natural fragrance oils or modify some of their characteristics.

The present invention relates to certain terpene derivatives and more particularly to synthetic cyclopropane substituted cyclohexanes and cyclohexanols useful as flavors or fragrances.

The compounds of the invention fall within the scope of the following illustrative chemical structure:

In the structural formula shown, R is intended to represent hydrogen or a hydroxy radical, R stands for 2-hydroxyisopropyl or an alkyl radical of 1 to 4 carbon atoms but preferably methyl, with R standing for hydrogen and R representing an alkyl substituted cyclopropyl radical, or when R and R are taken together with a carbon of the cyclohexane ring, they represent a cyclopropyl or a dimethylcyclopropyl ring of a spiro (25) octane or spiro (2.5) octanol.

The compounds of the invention are synthesized from corresponding unsaturated compounds, which may be represented by the three cyclohexane derivatives shown below in which R, R and R have the previously indicated meanings. The starting materials represented by Formulae I, II and III are known compounds described in the text The Terpenes, by J. L. Simonsen, vol. 1, Cambridge University Press, New York (1953) and may be produced by procedures within the skill of the art.

Reaction of the unsaturated starting compounds with methylene iodide using a zinc-copper couple in an anhydrous ether solvent, following a procedure for the preparation of norcarane described by R. D. Smith and H. E.

3,770,836 Patented Nov. 6, 1973 ice Simmons in Organic Syntheses, vol. 41, pp. 72-75, John Wiley, New York (1961) will give rise to the corresponding cyclopropyl compounds of the invention. In the process described by the authors, the reaction is carried out with cyclohexene whereas the starting compounds utilized here are of the type in which the double bond is in a radical attached to a cyclohexane nucleus.

Preferred starting materials for preparing the compounds of the invention are p-menth-8-en-2-ol (dih'ydrocarveol), p-menth-S-en-l-ol (B-terpineol), p-menth-8-en-1, 2-diol, p-menth-4(8)-en-'1-ol ('y-terpineol), p-menth-4(8)- en-3-ol (pulegol), p-menth-8-en-3-ol (isopulegol), and 7-methylene-4-(2-hydroxyisopropyl) cyclohexane.

The following examples describe in greater detail the best mode for obtaining the compounds of the invention. It should be understood that these examples are given for illustrative purposes only and are not intended to be limitative of the invention.

EXAMPLE 1 To a slurry of 14.3 g. (0.22 g.-atom) of Zn(Cu) couple 1 in ml. of absolute ether was added acrystal of iodine and the mixture was stirred for 30 min. 30.8 g. (0.2 mole) of l-isopulegol and 59 g. (0.22 mole) of diiodo methane were added in one portion. The reaction mixture was then heated under reflux for 65 hours.

By this time the gray couple had turned to a copper color. The reaction was allowed to cool to room temperature, filtered, and the solid washed with two 50-ml. portions of absolute ether. The ether washings and filtrate were combined and washed with two 50-ml. portions of saturated ammonium chloride solution, two 50-ml. portions of saturated sodium bicarbonate solution and one SO-ml. portion of water. The ether solution was dried over anhydrous magnesium sulfate and the ether removed in vacuo to give a yellow-green oil. This oil was shown by vapor-phase chromatography to consist of a 50-50 mixture of the starting l-isopulegol and 5-methyl-2-(1- methylcyclopropyl) cyclohexanol.

An analytical sample was obtained by injecting 100 pl. samples onto the gas chromatography and trapping the desired material.

Analysis.--Calcd. for C H O (percent): C, 78.51; H, 11.98. Found (percent): C, 78.48; H, 12.12.

NMR in CDCl showed multiplets in the region 6 0.1- 2.1 integrating for 19 protons including one exchangeable proton (OH) at 6 2.1 and cyclopropane peaks at 6 0.1- 1

0.5. The methine proton The zinc-copper couple was prepared as described in Organic Synthesis, 41, 72 (1961).

Vapor phase chromatography was carried out in all cases on an F & M 500 Gas Chromatograph using a. 10 foot Carbowax column at 200 C.

A similar procedure may be used to prepare other compounds falling within the scope of the invention. Thus, one may replace the isopulegol with an equi-molar amount of dihydrocarveol, producing 2-methyl-5-(1 methylcyclopropyl) cyclohexanol; or with B-terpineol, producing l-methyl 4 (l-methylcyclopropyl) cyclohexanol; or with p-menth-8-en-1,2-di-ol, producing 1-methyl-4- (l-methylcyclopropyl) cyclohexan-1,2-diol.

The following example is illustrative of the best mode for obtaining spirooctanes.

EXAMPLE 2 To a slurry of 7.2 g. (0.11 g.-atorn) of Zn(Cu) couple in 50 ml. of absolute ether add a crystal of iodine and stir the mixture for 30 min. 15.4 g. (0.1 mole) of pulegol and 29.5 g. (0.11 mole) of diiodornethane are added in one portion. The reaction mixture is then heated under reflux for 65 hours.

The reaction miXture is cooled to room temperature, filtered, and the solid Washed with two 25-ml. portions of absolute ether. The ether washings and filtrate are combined and washed with two 25-ml. portions of saturated ammonium chloride solution, two ZS-ml. portions of saturated sodium bicarbonate solution and one 25-ml. portion of water. The ether solution is dried over anhydrous magnesium sulfate and the ether removed in vacuo to give an Oil.

This oil is purified by distillation and is identified by analytical and spectral data as either 1,1,6-trimethylspiro[2.5]octan-4-ol or by other terminology, S-methyl- 2-( 2,2-dirnethy1cyclopropyl) cyclohexanol. It has a pleasant aroma and is useful as a fragrance or odorant.

In the same way, but starting with the molar equivalent of p-menth-4(8)-en-1-ol -terpineol) the compound produced would be 1,1,6-trimethyl-spiro [2.5] octan-6-ol; and starting with the molar equivalent of 1-methylene-4-(2- hydroxyisopropyl) cyclohexane, the compound produced would be 6-(Z-hydroxyisopropyl)spiro [2.5] octane.

All of the compounds of the invention are ifragrances useful for various commercial applications in the same manner as the terpenes from which they have been derived.

The invention that is claimed is:

1. The compound, 5-methyl-2-(l-methylcyclopropyl) cyclohexanol.

2. The compound, 2-methyl-5-(l-methylcyclopropyl) cyclohexanol.

3. The compound, 1-methyl-4-(l-methylcyclopropyl) cyclohexanol.

References Cited Carlson et al.: Che-m. Abst, 71, 112169j, 1969. Perraud et a1.: Chem. Abst., 71, 12380c, 1969.

HOWARD T. MARS, Primary Examiner US. Cl. X.R. 

